This is a proposal for a new multi-categorical General Clinical Research Center at the Children's and University Hospitals. This proposal combines two previously funded GCRCs into a single unit. We plan to perform studies utilizing inpatient and outpatient and Core Laboratory facilities at the Children's Hospital GCRC unit with scatter beds at the University Hospital. This application includes proposals from the Departments of Pediatrics, Medicine, Surgery, Obstetrics/Gynecology, and Radiology. Major areas of research include: 1. Pediatric Liver Disease. Studies will define the pathophysiology of new inborn errors of bile acid metabolism, use ursodeoxycholic acid for treatment of cholestatic liver disease, and define the mechanism of growth failure and bone disease in chronic cholestasis. 2. Diabetes Mellitus. Studies will evaluate the relationship between proinsulin and insulin secretion/sensitivity in noninsulin-dependent diabetes mellitus, the natural history of diabetic nephropathy, and the autonomic dysfunction and responsiveness to hypoglycemia during pregnancy. 3. Bone Disease. Studies will examine the relationship between race and activity and bone mineralization in infants, the effect of lactation on calcium homeostasis, and bone mineralization in chronic pediatric diseases. 4. Growth Hormone. Studies of growth hormone (GH) will include the role of sexual dimorphism in growth hormone feedback regulation, the use of GH to promote growth in children with intrauterine growth retardation, and IGF-1 administration to children with growth hormone insensitivity. 5. Gaucher Disease. Clinical and molecular studies of Gaucher Disease and treatment with enzyme augmentation will be performed. 6. Cancer Prevention and Treatment. Studies will evaluate the bioavailability of soy isoflavones which may have specific anti- neoplastic qualities and use of specific radionuclides in cancer treatment. 7. Transplantation Immunology. The mechanism by which donor-specific blood or marrow transfusion favorably affects renal allograft survival will be evaluated.